Tumor-derived exosomes as mediators of disease and potential diagnostic biomarkers

Issue title: Biomarkers for Ovarian Cancer: New Technologies and Targets to Address Persistently Unmet Needs

Guest editors: Michael A. Tainskyx and Anna Lokshiny

Article type: Research Article

Authors: Roberson, Carolyn D.^{a; c; 1} | Atay, Safinur^{a; c; 1} | Gercel-Taylor, Cicek^{a; b} | Taylor, Douglas D.^{a; b; *}

Affiliations: [a] James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA | [b] Department of Obstetrics, Gynecology and Women's Health, University of Louisville School of Medicine, Louisville, KY, USA | [c] Department of Microbiology & Immunology, University of Louisville School of Medicine, Louisville, KY, USA | [x] Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, 540 East Canfield Avenue, Detroit, MI, USA | [y] University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, PA, USA

Correspondence: [*] Corresponding author: Dr. Douglas Taylor, Division of Gynecologic Oncology, James Graham Brown Cancer Center, University of Louisville School of Medicine, 505 S. Hancock Street, CTRB 316, Louisville, KY 40202, USA. E-mail: [email protected].

Note: [1] Authors contributed equally.

Abstract: Tumor cells release membranous structures, defined as microvesicles or exosomes, consisting of an array of macromolecules derived from the originating cells, including proteins, lipids, and RNA. The expression of antigenic molecules recognizable by T cells originally suggested a role for these vesicles as a cell-free antigen source for anti-cancer vaccines; however, evidence demonstrates that tumor exosomes can exert a broad array of detrimental effects on the immune system – ranging from apoptosis of activated cytotoxic T cells to impairment of monocyte differentiation into dendritic cells, to induction of myeloid-suppressive cells. Immunosuppressive exosomes of tumor origin can be found in neoplastic lesions and biologic fluids from cancer patients, implying a potential role of these pathways in in vivo tumor progression and systemic paraneoplastic syndromes. Through the expression of molecules involved in angiogenesis promotion, stromal remodeling, signaling pathway activation through growth factor/receptor transfer, chemoresistance, and intercellular genetic exchange, tumor exosomes could represent a central mediator of the tumor microenvironment. Their release by tumor cells may represent the future for targeting therapeutic interventions and for development of multiplexed diagnostic biomarkers.

Keywords: Exosomes, cancer, biomarkers, biogenesis, intercellular communication

DOI: 10.3233/CBM-2011-0211

Journal: Cancer Biomarkers, vol. 8, no. 4-5, pp. 281-291, 2011